Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gladstone Scientists identify key mechanism involved in Type 2 diabetes

29.03.2012
Findings may lead to new strategies to address insulin resistance

Scientists at the Gladstone Institutes have discovered a key protein that regulates insulin resistance—the diminished ability of cells to respond to the action of insulin and which sets the stage for the development of the most common form of diabetes. This breakthrough points to a new way to potentially treat or forestall type 2 diabetes, a rapidly growing global health problem.

In a paper being published online this week in the Proceedings of the National Academy of Sciences, researchers in the laboratory of Gladstone Investigator Katerina Akassoglou, PhD, describe an unexpected role of the p75 neurotrophin receptor in controlling how the body processes sugar. Called p75NTR, this receptor protein is usually associated with functions in neurons.

"We identified that p75NTR is a unique player in glucose metabolism," said Dr. Akassoglou, who is also an associate professor of neurology at the University of California, San Francisco, with which Gladstone is affiliated. "Therapies targeted at p75NTR may represent a new therapeutic approach for diabetes."

The pancreas makes a hormone called insulin that processes glucose, moving it from the bloodstream into the body's cells where it is used for energy. Insulin resistance is a key feature of Type 2 diabetes, in which glucose builds up in the bloodstream and the body's cells are unable to function properly. According to the Centers for Disease Control and Prevention, more than 20 million Americans have type 2 diabetes.

"Type 2 diabetes has become a very serious health problem and it is increasing at an alarming rate," said Lennart Mucke, MD, who directs the institute in which the research was conducted. "These findings provide an important new avenue for developing better therapies to combat this deadly disease—the seventh leading cause of death in the United States."

Complex signaling interactions between several different types of tissue—including fat, liver, muscle and brain—regulate glucose metabolism. Because p75NTR is found in fat and muscle tissue and participates in many important functions in the cell, Gladstone scientists hypothesized that p75NTR might also help to regulate glucose metabolism.

To study this, the researchers used mice that lacked the genes for p75NTR. They compared these mice to normal mice and discovered that those lacking p75NTR were more responsive to insulin when fed a normal diet. Second, they used some molecular biology tricks to block the action of the p75NTR protein in fat cells. This also resulted in increased glucose absorption in response to insulin. In contrast, when they caused the fat cells to make more p75NTR, glucose absorption was reduced. Additionally, the researchers found that another important regulatory molecule, Rab5, played a key role in p75NTR's impact on metabolism.

"Importantly, regulation by p75NTR enhanced insulin's effectiveness in normal lean mice on a normal diet," said Bernat Baeza-Raja, PhD, postdoctoral fellow and lead author of the study. "Because these mice already process glucose efficiently, the actions of p75NTR on glucose transport indicate a direct role of this protein in the regulation of glucose metabolism."

"Our studies of p75NTR's unanticipated role in regulating glucose metabolism suggest a new target for drug therapies," said Dr. Akassoglou. "Future work is needed to test whether this finding may translate into a potential treatment."

This study was a collaborative work between scientists at Gladstone, the University of California, San Diego (UCSD), the University of Michigan and the University of Houston. Other scientists who participated in this research at Gladstone include Natacha Le Moan, PhD, Christian Schachtrup, PhD, Dimitrios Davalos, PhD, and Eirini Vagena. Jerrold Olefsky, PhD, and Pingping Li, PhD, at UCSD were co-senior and co-first authors, respectively. Funding was provided by a variety of sources, including the National Institutes of Health, the University of California San Francisco Liver Center and Diabetes and Endocrinology Center and the R. A. Welch Foundation.

About the Gladstone Institutes

Gladstone is an independent and nonprofit biomedical-research organization dedicated to accelerating the pace of scientific discovery and innovation to prevent, treat and cure cardiovascular, viral and neurological diseases. Gladstone is affiliated with the University of California, San Francisco.

Diane Schrick | EurekAlert!
Further information:
http://www.ucsf.edu

More articles from Life Sciences:

nachricht Polymers get caught up in love-hate chemistry of oil and water
28.02.2020 | DOE/Oak Ridge National Laboratory

nachricht How do zebrafish get their stripes? New data analysis tool could provide an answer
28.02.2020 | Brown University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: High-pressure scientists in Bayreuth discover promising material for information technology

Researchers at the University of Bayreuth have discovered an unusual material: When cooled down to two degrees Celsius, its crystal structure and electronic properties change abruptly and significantly. In this new state, the distances between iron atoms can be tailored with the help of light beams. This opens up intriguing possibilities for application in the field of information technology. The scientists have presented their discovery in the journal "Angewandte Chemie - International Edition". The new findings are the result of close cooperation with partnering facilities in Augsburg, Dresden, Hamburg, and Moscow.

The material is an unusual form of iron oxide with the formula Fe₅O₆. The researchers produced it at a pressure of 15 gigapascals in a high-pressure laboratory...

Im Focus: From China to the South Pole: Joining forces to solve the neutrino mass puzzle

Study by Mainz physicists indicates that the next generation of neutrino experiments may well find the answer to one of the most pressing issues in neutrino physics

Among the most exciting challenges in modern physics is the identification of the neutrino mass ordering. Physicists from the Cluster of Excellence PRISMA+ at...

Im Focus: Therapies without drugs

Fraunhofer researchers are investigating the potential of microimplants to stimulate nerve cells and treat chronic conditions like asthma, diabetes, or Parkinson’s disease. Find out what makes this form of treatment so appealing and which challenges the researchers still have to master.

A study by the Robert Koch Institute has found that one in four women will suffer from weak bladders at some point in their lives. Treatments of this condition...

Im Focus: A step towards controlling spin-dependent petahertz electronics by material defects

The operational speed of semiconductors in various electronic and optoelectronic devices is limited to several gigahertz (a billion oscillations per second). This constrains the upper limit of the operational speed of computing. Now researchers from the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg, Germany, and the Indian Institute of Technology in Bombay have explained how these processes can be sped up through the use of light waves and defected solid materials.

Light waves perform several hundred trillion oscillations per second. Hence, it is natural to envision employing light oscillations to drive the electronic...

Im Focus: Freiburg researcher investigate the origins of surface texture

Most natural and artificial surfaces are rough: metals and even glasses that appear smooth to the naked eye can look like jagged mountain ranges under the microscope. There is currently no uniform theory about the origin of this roughness despite it being observed on all scales, from the atomic to the tectonic. Scientists suspect that the rough surface is formed by irreversible plastic deformation that occurs in many processes of mechanical machining of components such as milling.

Prof. Dr. Lars Pastewka from the Simulation group at the Department of Microsystems Engineering at the University of Freiburg and his team have simulated such...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

70th Lindau Nobel Laureate Meeting: Around 70 Laureates set to meet with young scientists from approx. 100 countries

12.02.2020 | Event News

11th Advanced Battery Power Conference, March 24-25, 2020 in Münster/Germany

16.01.2020 | Event News

Laser Colloquium Hydrogen LKH2: fast and reliable fuel cell manufacturing

15.01.2020 | Event News

 
Latest News

New molten metal hybrid filters from TU Freiberg will make components even safer and more resistant in the future

28.02.2020 | Materials Sciences

Polymers get caught up in love-hate chemistry of oil and water

28.02.2020 | Life Sciences

Two NE tree species can be used in new sustainable building material

28.02.2020 | Architecture and Construction

VideoLinks
Science & Research
Overview of more VideoLinks >>>